Flavonoids are abundant throughout nature and exert a broad range of biological activities in plants and animals. There are now considered to be over 4,000 flavonoids existent in nature. These compounds are the primary source for the colors that occur in the fall in many flowers and trees. Flavonoids are found in fruits, vegetables, nuts, seeds, herbs, spices, stems, flowers, red wine, cocoa, and tea, and are consumed on a regular basis in the human diet. These compounds can be classified according to their substituents into flavanols, anthocyanidins, flavones, flavanones, and chalcones. Some of the biological activities of flavonoids include anti-inflammatory, antiviral, antifungal, antibacterial, estrogenic, anti-oxidant, antiallargenic, anticarcinogenic, antithrombotic, hepatoprotective, and antiproliferative.
Some of the principle flavonoids that have been studied and found to have potential as therapeutic agents include flavonoids or flavanols from green tea and cocoa (or dark chocolate) such as epigallocatechin gallate, epigallocatechin, epicatechin, catechin, and epicatechin gallate, flavonoids from grape-type fruits or berries such as resveratrol (3,5,4′-trihydroxystilbene), pterostilbene derived from natural sources such as blueberries, grapes, and other berries, or other botanical sources. They can also be produced synthetically as 98% pterostilbene, compounds from soy, such as genistein and diadzein, and quercetin, the richest source of which is onions. Pterostilbene, or 3,5-Dimethoxy-4-stilbenol or dimethoxyresveratrol (CAS#537-42-8), has a molecular weight of 256.299, and is also a lipophilic compound, making it insoluble in water. Pterostilbene has different pharmacokinetic properties due to differences in the way it is metabolized compared to resveratrol, and therefore has a longer half-life (stays in the blood-steam longer).
Other natural compounds found to be beneficial for health include lutein (extracted from marigold flowers, lycopene (extracted from tomatoes), curcumin (for example 1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 99% by HPLC), turmeric, co-enzyme Q-10 (ubidecarenone, ubiquinone, ubiquinol), epigallocatechin gallate (EGCG) derived from green tea, (−)-epicatechin from cocoa powder, essential oils such as citrus essential oils, grapefruit seed extracts, D-limonene, and other lipophilic flavor essential oils or natural compounds, carotenoids, astaxanthin, and phosphatidylserine. These lipophilic compounds can be classified as nutraceutical compounds or natural flavor essences because they are derived from nature and can be used therapeutically. These compounds typically will not soluble in water, and tend to float on water, and will not form a stable water soluble solution that is crystal clear and remains that way over time.
In order for any therapeutic molecular substance to be transported through the gastrointestinal tract, enter the blood, and eventually reach the organs and cells inside the body, the molecule should be finely dispersible or dissolvable in the aqueous phase of the intestinal fluid. Without dissolution, the drug will typically pass through the GI-tract. Flavonoids such as resveratrol are virtually insoluble in water, and animal pharmacokinetic studies of oral doses have demonstrated very low bioavailability. Likewise, human studies with green tea extracts standardized to the active catechins, have demonstrated very low absorption, usually less than 1% of the oral dose in animal or human studies. In fact, in one study, plasma tea catechin concentrations determined in humans after oral consumption of a green tea extract were 5-50 times less than the concentrations shown to exert biological activities in in vitro systems. Animal pharmacokinetic studies with trans-resveratrol also indicate less than 1-2% in plasma after an oral dose. No quercetin could be found in plasma after oral administration of up to 4 g in humans. Many flavonoids are lipophilic or fat soluble, and have very low solubility in water (hydrophobic). Only small amounts of resveratrol are contained in red wine. For example, resveratrol in wine may vary from 0.2 to 5.8 mg/liter. Co-enzyme Q-10 is a good example of a natural fat soluble compound that is hydrophobic, or insoluble in water and thus insoluble in water containing beverages such as juices or soft drinks.
Due to the many desirable properties of lipophilic natural compounds, it would be advantageous to have improved water soluble formulations and/or enhanced bioavailability formulations for dosing in vivo.